Neonatal Seizures
Conditions
Keywords
Neonates, Seizure
Brief summary
Current treatments for the brain damaging complication of neonatal seizures are unsatisfactory. A multi-centre Chinese clinical trials with the aim to using oral Levetiracetam to develop new treatment strategies for the treatment of neonatal seizures. The purpose of this study is to determine the correct oral dosing, safety and efficacy for oral Levetiracetam as first line treatment in term new born babies with seizures.
Detailed description
This project aims to improve the treatment of neonatal seizures. Current treatments are poorly effective and have significant side effects. Levetiracetam has great potential as a treatment for neonatal seizures but is not approved for use in children less than 1 years of age by oral. This study aims to obtain essential data regarding the efficacy and safety of oral Levetiracetam in neonatal population and simultaneously to use EEG monitoring systems that facilitate seizure detection and research. Specific aims are: 1. To determine the efficacy of oral Levetiracetam in terminating neonatal seizures by EEG in the Neonatal Neurological Intensive Care Unit (NNICU). 2. To determine dose escalation data by studying the additional efficacy of a further dose in non responders. 3. To determine additional pharmacokinetic data to confirm findings from our previous pharmacokinetic study. 4. To determine further safety data of oral Levetiracetam in neonates.
Interventions
Oral load of levetiracetam (50 mg/kg) following identification of EEG confirmed neonatal seizure.
Intravenous load of phenobarbital (20 mg/kg)following EEG confirmation of seizure activity load.
Sponsors
Xiamen Children's Hospital, Fujian of China
Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region
Guangzhou Women and Children's Medical Center
Second Affiliated Hospital of Wenzhou Medical University
Maternal and Child Health Hospital of Hubei Province
The Maternal & Children Health Hospital of Dehong, Yunnan of China
Children's Hospital of Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
No minimum to 28 Days
Healthy volunteers
No
Inclusion criteria
Neonatal seizure occurred and was proved by EEG according to abnormal discharge of brain. one or more of the following : 1. Male or female term baby with gestational \>37 weeks and postnatal age \< or= 28 days 2. Birthweight \>2500g 3. Written informed consent of parent or guardian
Exclusion criteria
1. Babies who have been close to death 2. Seizure occurred by metabolic factors (hypoglycemia, hypocalcemia, electrolyte disorder) 3. Babies who have received phenobarbitone or any other anticonvulsive medication before hospitalization 4. Abnormal renal function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| EEG | At Day 28 | Efficacy of levetiracetam by assessment of the change from baseline in EEG on Day 15. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neurodevelopment(Bayley Scores) | At Day 28 | Efficacy of levetiracetam by assessment of the change from baseline to Day 28 in neurodevelopment via Bayley Scores of Infant Development Mental Development Index (BSID). |
| Brain Parenchyma Alterations(MRI) | At Day 28 | Efficacy of levetiracetam by assessment of the change of brain from baseline in MRI on Day 28. |
| Seizure Control Days | From Day 1 to Day 28 post-dose in each period | Efficacy of levetiracetam by assessment of seizure control days. |
| Number of Adverse Events（Abnormal Appearance） | From Day 1 to Day 28 post-dose in each period | This is a composition of general appearance, abdomen, skin, head and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems. |
| Number of Adverse Events（Abnormal Blood Pressure） | From Day 1 to Day 28 post-dose in each period | — |
| Number of Adverse Events(Pulse) | From Day 1 to Day 28 post-dose in each period | — |
| Number of Adverse Events(Respiratory) | From Day 1 to Day 28 post-dose in each period | — |
| Number of Abnormal Clinical Chemistry | From Day 1 to Day 28 post-dose in each period | Safety of levetiracetam by assessment of safety laboratory tests. |
| Number of Abnormal Hematology | From Day 1 to Day 28 post-dose in each period | Safety of levetiracetam by assessment of safety laboratory tests. |
| Number of Abnormal Clinical Urinalysis | From Day 1 to Day 28 post-dose in each period | Safety of levetiracetam by assessment of safety laboratory tests. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Rate and extent of absorption by assessment of AUC(0-4) | At Day 1 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose) | Comparison of AUC(0-4) (Area under the plasma concentration-time curve from time zero to 4 hours after administration) of levetiracetam on Day 1 of each treatment period; up to 6 samples will be collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose). |
| Rate and extent of absorption by assessment of Cmax,ss of levetiracetam | At Day 14 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) | Comparison of Cmax,ss (observed maximum plasma concentration at steady state) of levetiracetam on Day 14 of each treatment period; up to 10 samples will be collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose). |
| Rate and extent of absorption by assessment of AUC(0-24) of levetiracetam | At Day 14 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) | Comparison of AUC(0-24) (Area under the plasma concentration-time curve from time zero to 24 hours after administration) of levetiracetam on Day 14 of each treatment period; up to 10 samples will be collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose). |
| Rate and extent of absorption by assessment of tmax,ss of levetiracetam | At Day 14 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) | Comparison of tmax,ss (time to reach maximum plasma concentration at steady state) of levetiracetam on Day 14 of each treatment period; up to 10 samples will be collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose). |
| Rate and extent of absorption by assessment of Cavg,ss of levetiracetam | At Day 14 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) | Comparison of Cavg,ss (average plasma concentration during a dosing interval at steady state) of levetiracetam on Day 14 of each treatment period; up to 10 samples will be collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose). |
| Rate and extent of absorption by assessment of AUC(0-last) of levetiracetam | At Day 1 and Day 14 in each period (in subjects with intensive pharmacokinetic assessments, on Day 1 at pre-dose and 15 and 30 minutes, and 1, 2 and 4 h post-dose, on Day 14 at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) | Comparison of AUC(0-last) (Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration) of levetiracetam (i.e. in subjects with intensive pharmacokinetic assessments) |
| Rate and extent of absorption following multiple dose administration by assessment of Cmin of levetiracetam | At Day 1 and on Day 14 at pre-dose in each period | Comparison of Cmin (predose concentration) of levetiracetam in each treatment period. |
| Rate and extent of absorption by assessment of Cmax | At Day 1 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose) | Comparison of Cmax (maximum observed plasma concentration) of levetiracetam on Day 1 of each treatment period; up to 6 samples will be collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose). |
| Rate and extent of absorption by assessment of tmax | At Day 1 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose) | Comparison of tmax (time to reach maximum plasma concentration) of levetiracetam on Day 1 of each treatment period; up to 6 samples will be collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose). |
Countries
China
Outcome results
None listed